A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes

Abstract

Objective: To evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).

Research design and methods: This 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A(1c) [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning.

Results: At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (-0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: -0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001).

Conclusions: In patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.

Trial registration: ClinicalTrials.gov NCT01027871.

Figures

Figure 1

A and B: Number of total and nocturnal hypoglycemia events per 100 patients over the 12-week treatment period. C and D: The rate of total and nocturnal hypoglycemia events based on A1C values over 12 weeks. The relationship between the hypoglycemia event rate during the treatment period and the end point A1C was characterized by the negative binomial regression curve of hypoglycemia event rate on the end point A1C. In A and B, the dashed line = insulin glargine and the solid line = LY2605541. In C and D, open circle = insulin glargine and closed circle = LY2605541.

Figure 2

Mean change in body weight with LY2605541 versus insulin glargine over 12 weeks. D, treatment difference. Solid line with closed circle = insulin glargine; dashed line with closed square = LY2605541.